Pharm. Pharmacol. Commun. 1999, 5: 591±594
Received May 25, 1999
Accepted August 13, 1999
# 1999 Pharm. Pharmacol. Commun.
Synthesis and In-vitro Antibacterial Activity of New
N-Substituted Piperazinyl Quinolones
A. FOROUMADI, S. EMAMI, P. HAGHIGHAT AND M. H. MOSHAFI
The Research Center of Kerman University of Medical Sciences, Kerman, Iran
Abstract
A series of N-[2-(2-furyl)-2-oxoethyl], N-[2-hydroxyimino-2-(2-furyl)ethyl], N-[2-(2-
furyl)-2-methoxyiminoethyl] and N-[2-(2-furyl)-2-phenylmethoxyiminoethyl] piperazinyl
quinolones were synthesized and evaluated for in-vitro antibacterial activity.
Compounds with a 2-(2-furyl)-2-oxoethyl group attached to the piperazine ring had
similar antibacterial activity to the reference drugs, nor¯oxacin and cipro¯oxacin, against
staphylococci, but signi®cantly decreased activity against Gram-negative bacteria. If the
hydrogen of oxime was replaced with a methyl or benzyl group, in-vitro antibacterial
activity decreased against Gram-negative bacteria, but activity was similar against
staphylococci.
Generally, cipro¯oxacin derivatives were more active than nor¯oxacin derivatives.
The introduction of ¯uoroquinolones, such as
cipro¯oxacin and o¯oxacin, has been the most
important advance in the discovery of new anti-
microbial agents in the past decade. These agents
are attractive because of their bioavailability after
oral administration and relatively few side-effects.
They are primarily used for the treatment of
infections caused by Gram-negative bacteria. Pro-
mising new ¯uoroquinolones are being developed
that have a broader spectrum of antimicrobial
activity including, in some cases, effectiveness
against Gram-positive and anaerobic infections
(Mandell & Petri 1996).
organisms, has been reported (Cooper et al 1992).
We previously reported the synthesis of a series of
N-(2-oxyimino-2-phenylethyl)piperazinyl quino-
lone derivatives, with signi®cant antibacterial
activity against some Gram-positive and Gram-
negative organisms (Foroumadi et al 1997).
Here we report a new series of N-substituted
piperazinyl quinolone derivatives with certain
structural modi®cations containing a 2-furyl moi-
ety, as potential antibacterial agents.
Material and Methods
The compounds currently available for clinical
use are 4-quinolones containing a carboxylic acid
moiety in the 3 position of the basic structure. The
newer ¯uoroquinolones also contain a ¯uorine
substituent at the 6 position, and many of these
compounds contain a piperazine moiety at the 7
position. The inhibition of DNA gyrase and cell
permeability of the quinolones are greatly in¯u-
enced by the nature of the C-7 substituent
(Domagala et al 1986). In addition, substitution of
bulky functional groups is permitted at the C-7
position (Shen et al 1989). The synthesis of a series
of compounds having an oxime and a substituted
oxime attached to the pyrrolidine and piperidine
rings at the C-7 position of quinolone, which
showed selective activity against Gram-positive
Chemical procedures
Reaction of hydroxylamine hydrochloride, O-
methylhydroxylamine hydrochloride or O-benzyl-
hydroxylamine hydrochloride with a-bromo-2-
acetylfuran (3) in methanol at room temperature
afforded compounds 5a, 5b and 7, respectively
(Schumann et al 1964; Schaefer & Mangold 1982).
Reaction of quinolones 1, 2 with a-bromo-2-acetyl-
furan (3) or a-bromo-2-acetylfuran oximes (5a±b
and 7) without protection of the 3-carboxylic acid
of quinolones (Kondo et al 1986) in the presence of
sodium bicarbonate in dimethylformamide (DMF)
at room temperature yielded ketones 4a±b and
oximes 6a±d and 8a±b, respectively (Figure 1).
1
The compounds were characterized by H NMR,
IR spectroscopy and microanalysis. The purity of
Correspondence: A. Foroumadi, Department of Medicinal
Chemistry, Faculty of Pharmacy, Kerman, Iran.